Perfluoroalkyl bromides have been developed as non-toxic contrast agents which can function as synthetic oxygen carriers. Properties of perfluoroalkyl bromides which render them desirable in various biomedical applications include their non-toxicity, their stability in emulsions at relatively high concentrations and their relatively high vapor pressure. These properties allow perfluoroalkyl bromides to be eliminated expediently from a subject's body after intravascular administration. Preferred perfluoroalkyl bromides for biomedical applications include perfluorooctyl bromide (PFOB) and perfluorodecalin (PFD). PFOB-based emulsions are used often because of their stability at high concentrations and ability to be rapidly transported to and excreted from tissues.
However, even PFOB-based emulsions suffer some disadvantages and limitations. Various biomedical applications require the use of fluorocarbon fluids which have a shorter residence time within a patient and thus have even higher vapor pressures than that of PFOB. Further, the need exists for a fluorocarbon fluid which can be administered in even higher concentrations and lower volumes than those which are possible with PFOB. Finally, existing methods for making perfluoroalkyl bromides are inefficient and costly.
Perfluoroalkyl halides are generally produced in a two-step reaction between a perfluorocarbon acid and silver salts using a Hunsdiecker reaction, as shown below (see Haszeldine, R. N., The Reactions of Metal Salts of Acids With Halogens. Part III. Some Reactions of Salts of Fluorohalogenoacetates and of Perfluoro-acids, J. Chem. Soc. 4259 (1952)). ##STR1##
The product of the first reaction step is an intermediate compound, perfluoroalkyl hypohalite, which immediately decomposes to a perfluoroalkyl halide and carbon dioxide accompanied by a release of free radicals. For example, in the Hunsdiecker reaction a perfluorocarboxylic acid reacts with silver carbonate to form perfluoro silver acetate (R.sub.f --CO.sub.2 Ag). This first reaction product is then purified in the presence of bromine to form the unstable intermediate compound, perfluoroalkyl hypobromite (R.sub.f --CO.sub.2 Br), which then decomposes to perfluoroalkyl bromide and carbon dioxide. Disadvantages of this method include the use of relatively expensive and potentially biohazardous silver salts, the inefficiencies associated with the indirect production of the desired perfluoroalkyl halide compound, and an inability to control, e.g., thermodynamically, the reaction. This lack of control arises from the extreme reactivity of the R.sub.f radical with halogenating compounds, e.g., Br, which is important in determining specific yields of the perfluoroalkyl halide. Although less expensive Group I metals, including sodium and potassium, have been used in place of silver, the results and yields have still been unsatisfactory.